The adequate performance of macrophage function depends on the cellular events: (a) migration of cells into the site of injury; (b) local retention and (c) cellular differentiation into macrophages and activated macrophages. This proposal is concerned with complement derived stimuli which induce migration or local retention and their relationship to MIF (macrophage migration inhibitory factor). It is based on our peliminary observations which indicate that C5 cleavage products induce macrophage migration while cleavage products of factor B of the properdin pathway induce spreading and inhibition of migration. We also found that inflamatory macrophages, which spread rapidly do not migrate in an MIF type assay. Our aims are to confirm and extend these observations by: (a) studying the correlations between macrophage spreading, inhbition of migration and adhesiveness to a substrate on one hand and cellular locomotion on the other hand; (b) establishing the required temporal sequence of stimuli for enhancement and inhbition of migration and other macrophage functions and (c) examining the possibility that some MIF activities may involve generation of cleavage products of factor B which induce spreading. These experiments may clarify many important aspects of macrophage function and provide more rational concepts for immunotherapy in infections and tumors.